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1.
Zhongguo Zhong Yao Za Zhi ; 48(4): 1132-1136, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36872284

RESUMO

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.


Assuntos
COVID-19 , Humanos , Algoritmos , Bases de Dados Factuais , Prescrições , Extratos Vegetais
2.
Front Psychiatry ; 14: 1134427, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873198

RESUMO

Introduction: With rapid population aging in China, geriatric depression has imposed a heavy burden on public health and society. This study aimed to investigate the prevalence and influencing factors of depressive symptoms among community-dwelling older adults in China. The findings of this study will contribute to the early detection and effective interventions for older adults with depressive symptoms. Methods: A cross-sectional study was conducted among people aged ≥65 years old in urban communities in Shenzhen, China, in 2021. This study assessed depressive symptoms (Geriatric Depression Scale-5, GDS-5), physical frailty (FRAIL Scale, FS), and physical function (Katz index of independence in the Activities of Daily Living, ADL). Multiple linear regression was used to examine potential predictors of depressive symptoms. Results: A total of 576 participants aged 71.73 ± 6.41 years were included in the analysis. More than half of them were females (53.0%). The average score of GDS-5 was 0.57 ± 1.11, with 78 (13.61%) participants with depressive symptoms (≥2). The mean scores of FS and ADL were 0.80 ± 1.08 and 9.49 ± 1.67, respectively. The final regression model indicated that those who were living alone, less satisfied with their personal life, frailer, and with worse abilities in ADL had a higher level of depression symptoms (R2 = 0.406, p < 0.001). Conclusion: The prevalence of depressive symptoms is high in this urban community-dwelling older adults in China. Given the critical role of frailty and ADL on depressive symptoms, specific attention to psychological support should be paid to older adults who are living alone and with poor physical conditions.

3.
Polymers (Basel) ; 15(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36904330

RESUMO

Furan-based compounds are a new class of compounds characteristic of wide abundance, feasible availability, and environmental friendliness. Presently, polyimide (PI) is the best membrane insulation material in the world, which is widely used in the fields of national defense, liquid crystals, lasers, and so on. At present, most polyimides are synthesized using petroleum-based monomers bearing benzene rings, while furan-based compounds bearing furan rings are rarely used as monomers. The production of petroleum-based monomers is always associated with many environmental issues, and their substitution with furan-based compounds seems a solution to addressing these issues. In this paper, t-butoxycarbonylglycine (BOC-glycine) and 2,5-furandimethanol, bearing furan rings, were employed to synthesize BOC-glycine 2,5-furandimethyl ester, which was further applied for the synthesis of furan-based diamine. This diamine is generally used to synthesize bio-based PI. Their structures and properties were thoroughly characterized. The characterization results showed that BOC-glycine could be effectively obtained using different posttreatment methods. And BOC-glycine 2,5-furandimethyl ester could be effectively obtained by optimizing the accelerating agent of 1,3-dicyclohexylcarbodiimide(DCC) with either 1.25 mol/L or 1.875 mol/L as the optimum value. The PIs originated from furan-based compounds were synthesized and their thermal stability and surface morphology were further characterized. Although the obtained membrane was slightly brittle (mostly due to the less rigidity of furan ring as compared with benzene ring), the excellent thermal stability and smooth surface endow it a potential substitution for petroleum-based polymers. And the current research is also expected to shed some insight into the design and the fabrication of eco-friendly polymers.

4.
Front Cardiovasc Med ; 10: 1003546, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910518

RESUMO

Background: There is limited evidence about vessel wall healing response following implantation of next-generation drug-eluting stents (DES) in patients admitted with a non-ST elevation acute coronary syndrome (NSTE-ACS). Cumulative data indicate that optical coherence tomography (OCT) imaging can optimize percutaneous coronary intervention results and expedite stent endothelialization in the general population but there is lack of data in NSTE-ACS patients. Methods: The EXPECT study is an investigator-initiated, prospective, randomized trial to assess early vascular healing response following next-generation DES implantation in patients admitted with NSTE-ACS based on OCT guidance and evaluation. Sixty patients are randomized at 1:1:1 ratio to OCT-guided percutaneous coronary intervention (PCI) with 3-month follow-up OCT imaging (O3 group, n = 20), to angiography-guided PCI with 3-month follow-up OCT imaging (A3 group, n = 20) and to angiography-guided PCI with 6-month follow-up OCT imaging (A6 group, n = 20). The primary endpoint of the study is stent strut coverage rate at 3- or 6- month follow-up in the studied groups. The secondary endpoints of the study include OCT imaging endpoints, clinical endpoints, and molecular biology endpoints at the different time points. The clinical endpoints comprised of major cardiovascular adverse events and individual components. The molecular biology endpoints comprised of lipid levels and the levels of inflammatory indicators. Discussion: The findings of the EXPECT study are anticipated to provide novel insights into vessel wall healing in NSTE-ACS population following implantation of next-generation DES, underscore the value of OCT imaging in expediting strut coverage in this setting, and explore the potential of an early discontinuation of dual antiplatelet therapy (DAPT) in this population. Clinical Trial Registration: ClinicalTrials.gov, NCT04375319.

5.
Front Immunol ; 14: 1135096, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36911675

RESUMO

Background/Objectives: Autoimmune pancreatitis (AIP) is a distinct form of pancreatic inflammatory disease that responds well to glucocorticoid therapy. Knowledge on AIP has rapidly evolved over the past two decades. Based on bibliometric analysis, this study aimed to assess the research status of AIP over the past two decades and determine the research focus and emerging topics. Methods: AIP-related publications published between January 1, 2002, and June 6, 2022, were retrieved from the Web of Science Core Collection. Bibliometric data were analyzed using HisCite, VOSviewer, CiteSpace, and bibliometrix package. Annual output, leading countries/regions, active institutions and authors, core journals and references, and keywords of AIP were evaluated. Results: Overall, 1,772 publications were retrieved from 501 journals by 6,767 authors from 63 countries/regions. Japan published articles on AIP the most (n=728, 41.1%), followed by the United States (n=336, 19%), Germany (n=147, 8.3%), China (n=127, 7%), and Italy (n=107, 6%). The top three most prolific authors were Terumi Kamisawa from Tokyo Metropolitan Komagome Hospital (n=117), Kazuichi Okazaki from Kansai Medical University (n=103), and Shigeyuki Kawa from Matsumoto Dental University (n=94). Pancreas was the most productive journal regarding AIP research (n=95), followed by the Journal of Gastroenterology (n=67), Internal Medicine (n=66), Pancreatology (n=63), and World Journal of Gastroenterology (n=62). "Diagnosis" was the most mentioned keyword. "Risk," "malignancy," "outcome," "22-gauge needle," and "fine-needle aspiration" were recognized as emerging topics. Conclusion: Japan was the leading country in AIP research. Research papers were mainly published in specialized journals. Diagnosis was the research focus. Long-term outcomes and pancreatic tissue acquisition were recognized as research frontiers for AIP.


Assuntos
Pancreatite Autoimune , Pancreatopatias , Humanos , Pâncreas , Bibliometria , China , Alemanha
6.
J Med Chem ; 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36880691

RESUMO

Nowadays, small-molecule drugs have become an indispensable part of tumor immunotherapy. Accumulating evidence has indicated that specifically blocking PGE2/EP4 signaling to induce robust antitumor immune response represents an attractive immunotherapy strategy. Herein, a 2H-indazole-3-carboxamide containing compound 1 was identified as a EP4 antagonist hit by screening our in-house small-molecule library. Systematic structure-activity relationship exploration leads to the discovery of compound 14, which displayed single-nanomolar EP4 antagonistic activity in a panel of cell functional assays, high subtype selectivity, and favorable drug-like profiles. Moreover, compound 14 profoundly inhibited the up-regulation of multiple immunosuppression-related genes in macrophages. Oral administration of compound 14, either as monotherapy or in combination with an anti-PD-1 antibody, significantly impaired tumor growth via enhancing cytotoxic CD8+ T cell-mediated antitumor immunity in a syngeneic colon cancer model. Thus, these results demonstrate the potential of compound 14 as a candidate for developing novel EP4 antagonists for tumor immunotherapy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36864250

RESUMO

BACKGROUND: It is well known that muscle disuse atrophy is associated with mitochondrial dysfunction, which is implicated in reduced nicotinamide adenine dinucleotide (NAD+ ) levels. Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in NAD+ biosynthesis, may serve as a novel strategy to treat muscle disuse atrophy by reversing mitochondrial dysfunction. METHODS: To investigate the effects of NAMPT on the prevention of disuse atrophy of skeletal muscles predominantly composed of slow-twitch (type I) or fast-twitch (type II) fibres, rabbit models of rotator cuff tear-induced supraspinatus muscle atrophy and anterior cruciate ligament (ACL) transection-induced extensor digitorum longus (EDL) atrophy were established and then administered NAMPT therapy. Muscle mass, fibre cross-sectional area (CSA), fibre type, fatty infiltration, western blot, and mitochondrial function were assayed to analyse the effects and molecular mechanisms of NAMPT in preventing muscle disuse atrophy. RESULTS: Acute disuse of the supraspinatus muscle exhibited significant loss of mass (8.86 ± 0.25 to 5.10 ± 0.79 g; P < 0.001) and decreased fibre CSA (3939.6 ± 136.1 to 2773.4 ± 217.6 µm2 , P < 0.001), which were reversed by NAMPT (muscle mass 6.17 ± 0.54 g, P = 0.0033; fibre CSA, 3219.8 ± 289.4 µm2 , P = 0.0018). Disuse-induced impairment of mitochondrial function were significantly improved by NAMPT, including citrate synthase activity (40.8 ± 6.3 to 50.5 ± 5.6 nmol/min/mg, P = 0.0043), and NAD+ biosynthesis (279.9 ± 48.7 to 392.2 ± 43.2 pmol/mg, P = 0.0023). Western blot revealed that NAMPT increases NAD+ levels by activating NAMPT-dependent NAD+ salvage synthesis pathway. In supraspinatus muscle atrophy due to chronic disuse, a combination of NAMPT injection and repair surgery was more effective than repair in reversing muscle atrophy. Although the predominant composition of EDL muscle is fast-twitch (type II) fibre type that differ from supraspinatus muscle, its mitochondrial function and NAD+ levels are also susceptible to disuse. Similar to the supraspinatus muscle, NAMPT-elevated NAD+ biosynthesis was also efficient in preventing EDL disuse atrophy by reversing mitochondrial dysfunction. CONCLUSIONS: NAMPT-elevated NAD+ biosynthesis can prevent disuse atrophy of skeletal muscles that predominantly composed with either slow-twitch (type I) or fast-twitch (type II) fibres by reversing mitochondrial dysfunction.

8.
Mol Neurobiol ; 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36940077

RESUMO

Excessive activation of aldose reductase (AR) in the brain is a risk factor for aggravating cerebral ischemia injury. Epalrestat is the only AR inhibitor with proven safety and efficacy, which is used in the clinical treatment of diabetic neuropathy. However, the molecular mechanisms underlying the neuroprotection of epalrestat remain unknown in the ischemic brain. Recent studies have found that blood-brain barrier (BBB) damage was mainly caused by increased apoptosis and autophagy of brain microvascular endothelial cells (BMVECs) and decreased expression of tight junction proteins. Thus, we hypothesized that the protective effect of epalrestat is mainly related to regulating the survival of BMVECs and tight junction protein levels after cerebral ischemia. To test this hypothesis, a mouse model of cerebral ischemia was established by permanent middle cerebral artery ligation (pMCAL), and the mice were treated with epalrestat or saline as a control. Epalrestat reduced the ischemic volume, enhanced BBB function, and improved the neurobehavior after cerebral ischemia. In vitro studies revealed that epalrestat increased the expression of tight junction proteins, and reduced the levels of cleaved-caspase3 and LC3 proteins in mouse BMVECs (bEnd.3 cells) exposed to oxygen-glucose deprivation (OGD). In addition, bicalutamide (an AKT inhibitor) and rapamycin (an mTOR inhibitor) increased the epalrestat-induced reduction in apoptosis and autophagy related protein levels in bEnd.3 cells with OGD treatment. Our findings suggest that epalrestat improves BBB function, which may be accomplished by reducing AR activation, promoting tight junction proteins expression, and upregulating AKT/mTOR signaling pathway to inhibit apoptosis and autophagy in BMVECs.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36966121

RESUMO

In this work, the high-activity (H2PO4-, Cr3+)-α-Fe2O3 (PCF) with abundant oxygen vacancies (OVs) and the high specific area was obtained by co-adding H2PO4- and Cr3+. Defect-enriched PCF/ß-In2S3 composites were prepared by low-temperature hydrothermal processes. The prepared composites exhibited improved photocatalytic degradation of 4-nitrophenol under visible light irradiation.The SO bond between PCF and ß-In2S3 promoted the formation of tight heterojunction composites and increased the OVs concentration. Under the synergistic effect of photo-Fenton, defects, and heterojunction, the PCF/ß-In2S3 composites effectively promoted the separation of photogenerated carriers and accelerated the production of active substances (•OH, •O2-, 1O2, and h+), leading to the improvement of photocatalytic-Fenton degradation performance. This work provided a new strategy for the preparation of highly efficient photocatalysts.

10.
Int J Pharm ; 636: 122821, 2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36914017

RESUMO

Breast cancer has become the malignant tumor with the largest incidence, especially the drug resistant triple negative breast cancer (TNBC). The combination therapeutic system can play a better role in resisting drug resistant TNBC. In this study, dopamine and tumor targeted folic acid modified dopamine were synthesized as carrier materials to construct melanin-like tumor targeted combination therapeutic system. The optimized nanoparticles of CPT/Fe@PDA-FA10 with efficient loading of camptothecin and iron was achieved, which showed tumor targeted delivery ability, pH sensitive controlled release, effective photothermal conversion performance and excellent anti-tumor efficacy in vitro and in vivo. CPT/Fe@PDA-FA10 plus laser could significantly kill the drug resistant tumor cells, inhibit the growth of the orthotopic drug resistant triple negative breast cancer through apoptosis/ferroptosis/photothermal treatment, and had no significant side effects on the main tissues and organs. This strategy provided a new idea for the construction and clinical application of triple-combination therapeutic system as effective treatment for drug resistant triple negative breast cancer.

11.
Adv Drug Deliv Rev ; : 114793, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36963569

RESUMO

Surgery and drug therapy are the two principal options for cancer treatment. However, their clinical benefits are hindered by the difficulty of accurate location of the tumors and timely monitoring of the treatment efficacy of drugs, respectively. Rapid development of imaging techniques provides promising tools to address these challenges. Compared with conventional imaging techniques such as magnetic resonance imaging and computed tomography etc., fluorescence imaging exhibits high spatial resolution, real-time imaging capability, and relatively low costs devices. The advancements in fluorescent probes further accelerate the implementation of fluorescence imaging in tumor diagnosis and treatment monitoring. In particular, the emergence of site-specifically activatable fluorescent probes fits the demands of tumor delineation and real-time feedback of the treatment efficacy. A variety of small molecule probes or nanoparticle-based probes have been developed and explored for the above-mentioned applications. This review will discuss recent advances in fluorescent probes with a special focus on activatable nanoprobes and highlight the potential implementation of activatable nanoprobes in fluorescence imaging-guided surgery as well as imaging-guided drug therapy.

12.
Ecol Lett ; 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36958943

RESUMO

Global greening, characterized by an increase in leaf area index (LAI), implies an increase in foliar carbon (C). Whether this increase in foliar C under climate change is due to higher photosynthesis or to higher allocation of C to leaves remains unknown. Here, we explored the trends in foliar C accumulation and allocation during leaf green-up from 2000 to 2017 using satellite-derived LAI and solar-induced chlorophyll fluorescence (SIF) across the Northern Hemisphere. The accumulation of foliar C accelerated in the early green-up period due to both increased photosynthesis and higher foliar C allocation driven by climate change. In the late stage of green-up, however, we detected decreasing trends in foliar C accumulation and foliar C allocation. Such stage-dependent trends in the accumulation and allocation of foliar C are not represented in current terrestrial biosphere models. Our results highlight that a better representation of C allocation should be incorporated into models.

13.
Urol Oncol ; 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-36967252

RESUMO

OBJECTIVE: To assess the effects of metabolic syndrome (MetS) and its components on the survival and prognosis of patients with localized clear cell renal cell carcinoma (ccRCC). DESIGN AND METHODS: This retrospective cohort study in Chongqing, China, identified patients with localized ccRCC from two medical centers of Chongqing Medical University between January 1, 2011, and December 31, 2020. The Chinese Medical Association Diabetes Society criteria of 2004 were used to diagnose MetS. Univariate and multivariate Cox proportional hazards regression analyses were conducted to identify independent risk factors for ccRCC. The outcomes were overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS). RESULTS: In our cohort, 378 eligible patients with localized ccRCC were included (median age, 56; range, 30-85; 255 men [67.5%]), and 87 patients (23.0%) were diagnosed with MetS. The median follow-up time was 66 months (1-126 months). Kaplan-Meier and log-rank analyses showed shorter PFS (P = 0.043) and CSS (P = 0.009) in patients with MetS. Univariate and multivariate Cox regression analyses found that MetS and dyslipidemia were independent risk factors for CSS in patients with localized ccRCC (P = 0.047; P = 0.035). When we analyzed MetS separately, the 4 components of MetS (hypertension, hyperglycemia, overweight/obesity, and dyslipidemia) did not show significant differences in OS, PFS, and CSS. CONCLUSION: MetS and dyslipidemia are independent adverse prognostic factors for CSS in patients with localized ccRCC. It is suggested to assign comprehensive therapy and follow-up to this patient population.

14.
J Alzheimers Dis ; 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36970911

RESUMO

BACKGROUND: Olfactory dysfunction appears prior to cognitive decline, and thus it has been suggested to be an early predictor of Alzheimer's disease. However, it is currently not known whether and how olfactory threshold test could serve as a quick screening tool for cognitive impairment. OBJECTIVE: To define olfactory threshold test for screening cognitive impairment in two independent cohorts. METHODS: The participants are comprised of two cohorts in China, 1,139 inpatients with type 2 diabetes mellitus (T2DM, Discovery cohort) and 1,236 community-dwelling elderly (Validation cohort). Olfactory and cognitive functions were evaluated by Connecticut Chemosensory Clinical Research Center test and Mini-Mental State Examination (MMSE), respectively. Regression analyses and receiver operating characteristic (ROC) analyses were carried out to determine the relation and discriminative performance of the olfactory threshold score (OTS) regarding identification of cognition impairment. RESULTS: Regression analysis showed that olfactory deficit (reducing OTS) was correlated with cognitive impairment (reducing MMSE score) in two cohorts. ROC analysis revealed that the OTS could distinguish cognitive impairment from cognitively normal individuals, with mean area under the curve values of 0.71 (0.67, 0.74) and 0.63 (0.60, 0.66), respectively, but it failed to discriminate dementia from mild cognitive impairment. The cut-off point of 3 showed the highest validity for the screening, with the diagnostic accuracy of 73.3% and 69.5%. CONCLUSION: Reducing OTS is associated with cognitive impairment in T2DM patients and the community-dwelling elderly. Therefore, olfactory threshold test may be used as a readily accessible screening tool for cognitive impairment.

15.
Neurosurg Focus ; 54(3): E5, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36857791

RESUMO

OBJECTIVE: Foramen magnum decompression with duraplasty (FMDD) is one of the most frequently utilized surgical treatments for Chiari malformation type I (CMI) in adults. However, its long-term outcomes remain controversial. The object of this study was to evaluate the long-term outcomes of FMDD in adults with CMI. METHODS: In total, 297 adults with CMI who had undergone FMDD at the authors' institution between 2011 and 2020 were included in this retrospective study. Long-term (> 1 year) outcomes were evaluated using the Chicago Chiari Outcome Scale (CCOS), visual analog scale (VAS), and Japanese Orthopaedic Association (JOA) scale. RESULTS: The median patient age was 44 years (range 18-65 years). The mean clinical follow-up period was 67 months (range 14-123 months). Compared with preoperative conditions, the postoperative syringomyelia regression rate was 91.3% (242/265), and the cerebellar tonsil ascended in 18.2% of patients (54/297), was stable in 64.3% (191/297), and continuously descended in 17.5% (52/297). Long-term clinical follow-up data were acquired from 267 patients. According to the CCOS score, the patient's condition improved in 62.5% of cases (167/267), was stable in 31.8% (85/267), and worsened in 5.6% (15/267). According to the VAS score, the patient's condition improved in 59.5% of cases (110/185), remained unchanged in 27.6% (51/185), and worsened in 13.0% (24/185) among the follow-up patients with relevant data. According to the JOA score, the patient's condition improved in 40.1% of cases (107/267), remained unchanged in 50.2% (134/267), and worsened in 9.7% (26/267). Notably, there was no association between clinical outcomes and syringomyelia regression (p = 0.227) or changes in the cerebellar tonsillar position (p = 0.323). CONCLUSIONS: FMDD is a simple, safe, and effective surgical procedure for adult CMI that yields significant and sustained improvement in clinical and radiological outcomes. However, clinical improvement does not always correlate with syringomyelia regression and cerebellar tonsillar shift.


Assuntos
Malformação de Arnold-Chiari , Siringomielia , Humanos , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Forame Magno , Estudos Retrospectivos , Descompressão
16.
Neurol Ther ; 2023 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-36870011

RESUMO

BACKGROUND: Results from observational studies indicate an association between circulating levels of mammalian target of rapamycin (mTOR)-dependent circulating proteins and the risk of multiple sclerosis (MS). However, a causal association has not been fully elucidated. Mendelian randomization (MR) is used to overcome limitations inherent to observational studies, assess the causal association, and minimize bias due to confounding and reverse causation. METHODS: To explore the causal association between seven mTOR-dependent proteins (AKT, RP-S6K, eIF4E-BP, eIF4A, eIF4E, eIF4G, and PKC-α) and MS, we obtained summary statistics from the genome-wide association study (GWAS) meta-analysis of the International Multiple Sclerosis Genetics Consortium (47,429 patients and 68,374 controls) and the INTERVAL study (genetic associations with 2994 plasma proteins from 3301 healthy individuals). MR analyses were conducted using inverse variance weighted, weighted median estimator, and MR-Egger regression methods/models. Sensitivity analyses were performed to ensure the reliability of the findings. Single nucleotide polymorphisms (SNPs) that are independent (r2 < 0.01) and strongly associated to minerals (p < 1e-5) were selected as instrumental variables. RESULTS: The results of the MR analyses revealed that among the seven mTOR-dependent proteins selected for study, the circulating level of PKC-α (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.82-0.98; P = 0.017) and RP-S6K (OR 1.12, 95% CI 1.00-1.25; P = 0.045) were associated with MS risk and that there was no sign of pleiotropy or heterogeneity. PKC-α was negatively related to MS, while RP-S6K was positively related to MS. No significant causation was found between the other proteins studied (AKT, eIF4E-BP, eIF4A, eIF4E, eIF4G) and MS. CONCLUSION: Molecules in the mTOR signaling pathway may bidirectionally regulate the occurrence and development of MS. PKC-α is a protective factor, while RP-S6K is a risk factor. Further explorations of pathways underlying the association between mTOR-dependent proteins and MS are required. PKC-α and RP-S6K might be used as future therapeutic targets for screening high-risk individuals and potentially improving opportunities for targeted prevention strategies.

17.
Neuroradiology ; 2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36862186

RESUMO

PURPOSE: This study compares the performance of a 4-min multi-echo in steady-state acquisition (MENSA) with a 6-min fast spin echo with variable flip angle (CUBE) protocol for the assessment of lumbosacral plexus nerve root lesions. METHODS: Seventy-two subjects underwent MENSA and CUBE sequences on a 3.0-T MRI scanner. Two musculoskeletal radiologists independently assessed the images for quality and diagnostic capability. A qualitative assessment scoring system for image quality and quantitative nerve signal-to-noise ratio (SNR) and iliac vein and muscle contrast-to-noise ratios (CNR) was applied. Using surgical reports as the reference, sensitivity, specificity, accuracy, and area under the receiver operating characteristic curves (AUC) were evaluated. Intraclass correlation coefficients (ICC) and weighted kappa were used to calculate reliability. RESULTS: MENSA image quality rating (3.679 ± 0.47) was higher than for CUBE images (3.038 ± 0.68), and MENSA showed higher mean nerve root SNR (36.935 ± 8.33 vs. 27.777 ± 7.41), iliac vein CNR (24.678 ± 6.63 vs. 5.210 ± 3.93), and muscle CNR (19.414 ± 6.07 vs. 13.531 ± 0.65) than CUBE (P < 0.05). Weighted kappa and ICC values indicated good reliability. Sensitivity, specificity, and accuracy of diagnosis based on MENSA images were 96.23%, 89.47%, and 94.44%, respectively, and AUC was 0.929, compared with 92.45%, 84.21%, 90.28%, and 0.883 for CUBE images. The two correlated ROC curves were not significantly different. Weighted kappa values for intraobserver (0.758) and interobserver (0.768-0.818) reliability were substantial to perfect. CONCLUSION: A time-efficient 4-min MENSA protocol exhibits superior image quality and high vascular contrast with the potential to produce high-resolution lumbosacral nerve root images.

18.
J Inflamm Res ; 16: 1059-1075, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936348

RESUMO

Background and Objectives: The prognosis is known to differ significantly among advanced gastric cancer (AGC) with Borrmann type III. This study aimed to evaluate the prognosis of these patients more individually. Methods: We selected 542 AGC patients with Borrmann type III. We used the receiver operating characteristic curve to analyze the cutoff values of inflammation indexes, and used Kaplan-Meier and Log rank tests to analyze recurrence-free survival (RFS) and overall survival (OS). The independent risk factors for recurrence and prognosis were analyzed by Cox proportional hazards regression model. The nomogram models were constructed by R studio. Results: Patients with high preoperative fibrinogen (F) and systemic immune-inflammation index (SII) levels had worse RFS and OS and higher risk of postoperative locoregional recurrence, hematogenous metastasis and lymph node metastasis. F and SII can combine with different clinicopathological features (all P<0.05) to construct nomograms to predict 5-year recurrence and prognosis, which both were superior to pTNM stage alone. Conclusion: The nomogram models based on F and SII can evaluate AGC with Borrmann type III postoperative recurrence and prognosis.

20.
Glob Chang Biol ; 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36929655

RESUMO

Monitoring and estimating drought impact on plant physiological processes over large regions remains a major challenge for remote sensing and land surface modeling, with important implications for understanding plant mortality mechanisms and predicting the climate change impact on terrestrial carbon and water cycles. The Orbiting Carbon Observatory 3 (OCO-3), with its unique diurnal observing capability, offers a new opportunity to track drought stress on plant physiology. Using radiative transfer and machine learning modeling, we derive a metric of afternoon photosynthetic depression from OCO-3 solar-induced chlorophyll fluorescence (SIF) as an indicator of plant physiological drought stress. This unique diurnal signal enables a spatially explicit mapping of plants' physiological response to drought. Using OCO-3 observations, we detect a widespread increasing drought stress during the 2020 southwest US drought. Although the physiological drought stress is largely related to the vapor pressure deficit (VPD), our results suggest that plants' sensitivity to VPD increases as the drought intensifies and VPD sensitivity develops differently for shrublands and grasslands. Our findings highlight the potential of using diurnal satellite SIF observations to advance the mechanistic understanding of drought impact on terrestrial ecosystems and to improve land surface modeling.

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